This application is the national phase under 35 U.S.C. xc2xa7371 of PCT International Application No. PCT/JP00/00314 which has an International filing date of Jan. 24, 2000, which designated the United States of America and was published in English.
The present invention relates to acrylamide derivatives having functional groups on side chains, homopolymers and copolymers of said derivatives, as well as crosslinked products of said polymers. Acrylamide derivatives of the present invention can readily be radical-polymerized to conveniently prepare homopolymers and can also be copolymerized with other monomers. Copolymers synthesized from acrylamide derivatives of the present invention can be temperature-responsive polymers, which are soluble below but insolubilized above a specific temperature in aqueous solutions. Thus, they can be immobilized on the surface of a solid to show hydrophilicity and hydrophobicity below and above the specific temperature, respectively. Copolymers of the present invention can be used not only to switch between hydrophilicity and hydrophobicity in a narrow temperature range but also to switch from an electrically charged state to a non-charged state simply by temperature change. Moreover, their various functional groups can be used to introduce various molecules via covalent or hydrogen bonds.
N-alkyl-substituted acrylamide polymers are one of temperature-responsive polymers, among which poly(N-isopropyl acrylamide) (hereinafter abbreviated as PIPAAm) is water-soluble below but rapidly insolubilized to form a precipitate above the phase transition temperature of 32xc2x0 C. Sequences of PIPAAm have been introduced into the surfaces of solids to switch between hydrophilicity and hydrophobicity simply by temperature change for harvesting cells after culture or development into chromatography. Such techniques are described in the following documents, for example:
T. Okano, N. Yamada, H. Sakai, Y. Sakurai, Journal of Biomedical Materials Research, vol. 27, pp. 1243-1251 (1993);
T. Okano, N. Yamada, M. Okuhara, H. Sakai, Y. Sakurai, Biomaterials, vol. 16, pp. 297-303 (1995);
H. Kanazawa, K. Yamamoto, Y. Matsushima, N. Takai, A. Kikuchi, Y. Sakurai, T. Okano, Analytical Chemistry, vol. 68, pp. 100-105 (1996);
H. Kanazawa, Y. Kashiwase, K. Yamamoto, Y. Matsushima, A. Kikuchi, Y. Sakurai, T. Okano, Analytical Chemistry, vol. 69, pp. 823-830 (1997).
These temperature-responsive polymers are commonly copolymerized with comonomers having a functional group such as acrylic acid to introduce the functional group into said polymers. However, straight-chain polymers or hydrogels (i.e. crosslinked products) incorporating an increased rate of acrylic acid inevitably showed a significant rise in phase transition temperature and insensitive transition behaviors. Namely, no method has existed for introducing many functional groups into temperature-responsive polymers or hydrogels while maintaining the sensitive temperature response.
An object of the present invention is to provide a monomer for preparing a polymer or hydrogel (i.e. crosslinked product) incorporating many functional groups while maintaining the sensitive temperature response, and said polymer or hydrogel (i.e. crosslinked product).
We carefully studied to solve the above problems. As a result, we found that the temperature response of homopolymers can be maintained by copolymerizing them with a monomer having a closely similar structure to that of the homopolymers, and thus attained the present invention.
Accordingly, the present invention provides acrylamide derivatives of the following general formula (I): 
wherein R1 represents a hydrogen atom, a straight-chain or branched alkyl group containing 1 to 6 carbon atoms or a C3-6 cycloalkyl group, R2 and R3 each independently represent an alkylene group containing 1 to 6 carbon atoms or R2 and R3 may be combined to form a ring, X represents a hydrogen atom, an amino group, a hydroxyl group, a halogen atom, a carboxyl group or a xe2x80x94COOR4 group wherein R4 represents a C1-6 straight-chain or branched alkyl, C3-6 cycloalkyl, phenyl, substituted phenyl, benzyl or substituted benzyl group, and Y represents an amino group, a hydroxyl group, a halogen atom, a carboxyl group or a xe2x80x94COOR4 group wherein R4 represents a C1-6 straight-chain or branched alkyl, C3-6 cycloalkyl, phenyl, substituted phenyl, benzyl or substituted benzyl group.
The present invention also provides polymers consisting of identical or different repeating units of the following general formula (II): 
wherein R1 represents a hydrogen atom, a straight-chain or branched alkyl group containing 1 to 6 carbon atoms or a C3-6 cycloalkyl group, R2and R3 each independently represent a alkylene group containing 1 to 6 carbon atoms or R2 and R3 may be combined to form a ring, X represents a hydrogen atom, an amino group, a hydroxyl group, a halogen atom, a carboxyl group or a xe2x80x94COOR4 group wherein R4represents a C1-6 straight-chain or branched alkyl, C3-6 cycloalkyl, phenyl, substituted phenyl, benzyl or substituted benzyl group, and Y represents an amino group, a hydroxyl group, a halogen atom, a carboxyl group or a xe2x80x94COOR4 group wherein R4represents a C1-6 straight-chain or branched alkyl, C3-6 cycloalkyl, phenyl, substituted phenyl, benzyl or substituted benzyl group.
The present invention also provides copolymers consisting of different or identical repeating units of the above general formula (II) and different or identical repeating units of general formula (III): 
wherein R1 represents a hydrogen atom, a straight-chain or branched alkyl group containing 1 to 6 carbon atoms or a C3-6 cycloalkyl group, R5 represents a straight-chain or branched alkyl group containing 1 to 6 carbon atoms or a C3-6 cycloalkyl group, and R6 represents a straight-chain or branched alkyl group containing 1 to 6 carbon atoms or a C3-6 cycloalkyl group, or R5 and R6 may be combined to form a 3-, 4-, 5 or 6-membered ring in which the xe2x80x94CHxe2x80x94 group to which they are attached is one member.
Additionally, the present invention provides crosslinked products containing said polymers and crosslinked products containing said copolymers.